Methods and architecture for power optimization of iontophoretic transdermal drug delivery

ABSTRACT

Embodiments of the invention provide an architecture, system and methods for optimizing power utilization for transdermal iontophoretic drug delivery which maintain a iontophoretic driving voltage at a reduced or even minimum value to support an iontophoretic delivery current. The reduced voltage reduces the power requirements for a transdermal iontohoretic delivery system during a period of drug delivery. Embodiments of an architecture for implementing this approach can utilize a controller which compares the desired current to the actual current and adjusts the voltage to reduce the amount of power used for iontophoretic drug delivery. The controller can comprise a state machine or microprocessor. Embodiments of the invention are particularly useful for extending the battery life of transdermal iontophoretic drug delivery systems.

RELATED APPLICATIONS

This application claims the benefit of priority of U.S. ProvisionalPatent Application Ser. No. 61/303,284, entitled “Methods andArchitecture for Power Optimization of Iontophoretic Transdermal DrugDelivery”, filed Feb. 10, 2010; which is fully incorporated by referenceherein for all purposes.

FIELD OF THE INVENTION

Embodiments described herein relate to methods for power optimizationfor transdermal drug delivery systems. More specifically, embodimentsdescribed herein relate to methods for power optimization ofiontophoretic transdermal drug delivery systems.

BACKGROUND

The typical form of treatment for a number of medical conditions such asdiabetes, iron deficiency anemia and cancer includes oral andintravenous drug delivery. However, both oral and intravenous forms ofdrug delivery treatment for these and other conditions have a number oflimitations. In many cases, oral delivery can have poor absorptionparticularly in the presence of other medications as well as a number ofside effects. Intravenous limitations include the requirement to mix andstore the medication in liquid form as well as the use of steriletechniques in administration. These can be particularly problematic inthird world countries where adequate refrigeration and sterile needlesare not readily available, limiting shelf life and exposing the patientto infection. Also, IV administration can include several risk factorsincluding anaphylaxis and cardiovascular complications. Thus, there is aneed for improved methods of drug delivery for many forms of treatment.

Transdermal iontophoresis is a non-invasive method of propelling highconcentrations of drug or other therapeutic agents through the skin byrepulsive electromotive force using a small electrical charge. In orderto facilitate ease of use to the patient, iontophoretic transdermaldevices are portable and thus include a portable power source such as abattery so that the device can be worn or carried by the patient.Further, in some instances it is desirable for such power sources to beable to provide power for a period of hours each day possibly overmultiple days in order to allow the patient to receive a selected drugduring this period. Thus battery life can be a factor in the usabilityof a transdermal iontophoretic delivery device for the patient so thatpatient need not change batteries over the course of a single treatmentor even over many treatments. Thus there is a need for approaches forimproving battery life for transdermal iontophoretic delivery devicesand systems.

BRIEF SUMMARY

Embodiments of the invention provide an architecture, system and methodfor optimizing power used for the transdermal iontophoretic delivery ofdrugs and other therapeutic agents. Many embodiments provide anarchitecture, system and method for optimizing power used for thetransdermal iontophoretic delivery of drugs and other therapeutic agentswherein the voltage used for driving transdermal iontophoresis (thedriving voltage) is adjusted responsive to electrical parameters in thearchitecture and/or electrical circuit used for transdermaliontophoretic drug delivery. Such parameters can include the actualiontophoretic current, the total or lumped (herein total)resistance/impedance of the iontophoretic transdermal delivery circuitor the tissue resistance/impedance at the iontophoretic delivery site.As used herein, resistance refers to embodiments using a direct currentfor the iontophoretic delivery current and impedance refers toembodiments using an alternating current for the iontophoretic deliverycurrent. In particular embodiments using an AC iontophoretic deliverycurrent, the driving voltage is adjusted responsive to the totalimpedance between two electrodes used for iontophoretic currentdelivery.

In various aspects, the invention provides an approach for optimizingpower utilization for transdermal iontophoretic drug delivery whichmaintains the iontophoretic driving voltage at the minimum value ittakes to support a desired iontophoretic delivery current. Since thetissue impedance can change over time (e.g., due to tissue heating andchanges the ion concentration in tissue), it is desirable to also changethe iontophoretic voltage. Embodiments of this approach can utilize acontroller which compares the desired delivery current to the actualdelivered current and adjusts the driving voltage such that power usedfor iontophoretic delivery is reduced and even minimized. This in turn,extends both battery life and the delivery period for iontophoretic drugdelivery. Thus, over the course of a drug delivery regimen of days, oreven up to one to two weeks, a user need not remove a wearableiontophoretic delivery system to change a battery. This improvescompliance with a particular drug delivery regimen and in turn, helps tomaintain the desired concentration of drug in the patient's body overthe course of a delivery period. This serves to improve clinicaloutcomes while reducing the incidence of over and/or under delivery ofdrug. Embodiments of the invention are particularly useful for improvingcompliance with drug delivery regimens over long periods of time such asthose used for iron deficiency anemia, chemotherapy, pain management,diabetes, hypertension, blood volume management and other relatedconditions and diseases.

In one aspect, the invention provides a method for optimizing power foriontophoretic transdermal delivery of a therapeutic agent to a patientcomprising applying a patch to a skin, with the patch comprising atherapeutic agent and at least one electrode. Typically, at least twoelectrodes will be applied, though three, four or even greater numbersmay applied. The electrodes are then coupled to a power sourcecomprising electrical circuitry and one or more portable batteries orother electrical storage means. Collectively, the patch and power sourcecomprise an iontophoretic delivery system and the power source, patchand patient's skin comprise an iontophoretic delivery circuit foriontophoretic delivery. A selected current is then delivered to the skinfrom the power source through the patch/electrode to transport thetherapeutic agent into the skin (using an electromotive force). Anelectrical parameter of the iontophoretic delivery circuit is thenmeasured. Typically, this will include either the actual currentdelivered to tissue (herein delivery current) or the totalresistance/impedance of the iontophoretic delivery circuit, though otherresistance/impedance values are also considered. The voltage used tosupply the delivery current to skin is adjusted responsive to themeasured electrical parameter, wherein the voltage is adjusted tomaintain the selected delivery current while minimizing power deliveredfrom the power source. In many embodiments, the delivery current is analternating current which can have a frequency in the range of 0.5 to100 hz. Typically, the power source is an electrochemical battery suchas a lithium or lithium ion or alkaline battery. The life of the batterycan be extended as a result of the minimized delivered power. Theminimized power can also be used to maintain the voltage and/or currentof the battery above a minimum level during a period of transdermaltherapeutic agent delivery. The delivery period can extend from severaldays, to a week or two or longer. In use, this approach allows thepatient to wear and/or use a transdermal iontophoretic delivery devicefor a period of days or weeks or longer without having to take off thedevice to replace the batteries. This in turn, improves patientcompliance with a medicinal regimen and helps maintain in vivoconcentrations of the selected therapeutic agent at therapeuticallyeffective levels improving clinical outcomes.

In another aspect the invention provides circuit architectures (hereinarchitectures) for optimizing power for the iontophoretic transdermaldelivery of a therapeutic agent comprising. In one embodiment thearchitecture comprises a first and second electrode, a power sourceoperably coupled with the first and second electrodes, a current sourceoperably coupled to at least one of the first and second electrodes, ameasurement device operably coupled to the current source and acontroller operably coupled to the measurement device and the powersource. At least one of the electrodes is positioned in or on orotherwise operably coupled to an iontphoretic transdermal patch fordelivering the therapeutic agent to the patient. The power source cancomprise a voltage source such as an electrochemical storage battery(e.g., lithium alkaline, etc.) and a voltage converter operably coupledto the voltage source. In such embodiments the controller can beoperable coupled to the voltage regulator. The controller can compriseone or more of a microprocessor or other digital controller, statedevice or other analog controller. The controller can also include logicfor utilizing an input from the measurement device to generate an outputsent to the voltage regulator so as to maintain current from the currentsource above a threshold level while minimizing power drawn from thepower source including the battery. For digital embodiments of thecontroller the logic can be incorporated into one or more softwaremodules which are operable on the controller and may resident within thecontroller or stored in a memory device coupled to the controller. Themeasurement device can be configured as an impedance (resistance)measurement device, a current measurement device or other relatedelectrical property measurement device known in the art and may useutilize Ohms law for measuring one or more electrical properties. Invarious embodiments the measurement device may include a resistor andoperational amplifier (herein op-amp) or other amplifier device/circuit.For digitally based embodiments of the controller, the measurementdevice may also include an analog to digital converter (herein an A/Dconverter) for converting output signals from the measurement deviceinto digital form. In such embodiments all components of the measurementdevice can be fabricated on a single integrated circuit. Also, all orportions of the entre architecture can be fabricated on a singleintegrated circuit such as an ASIC or other related circuit.

Further details of these and other embodiments and aspects of theinvention are described more fully below, with reference to the attacheddrawing figures.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 is a cross sectional view showing the three main layers of theskin, the epidermis, the dermis and subcutaneous tissue as well as thepassageways into the skin.

FIG. 2 is a lateral view of an embodiment of a system for thetransdermal iontophoretic delivery of various therapeutic agents usingdelivery and lateral electrodes.

FIG. 3 a is a schematic side view showing placement of an embodiment ofa transdermal iontophoretic patch device on the surface of the skin,wherein the device comprises an active electrode assembly and a returnelectrode assembly.

FIG. 3 b is a schematic side view showing placement of an embodiment oftransdermal iontophoretic patch device on the surface of the skin,wherein the device comprises two active electrode assemblies.

FIGS. 4 a and 4 b are side and top views showing an embodiment of a skinpatch including an active electrode and lateral electrodes.

FIG. 5 is a schematic view showing an embodiment of a power optimizingarchitecture for use with iontophoretic transdermal drug deliverysystems.

FIG. 6 is a flowchart of an algorithm of power optimization for use withiontophoretic transdermal drug delivery systems.

DETAILED DESCRIPTION OF THE INVENTION

Many embodiments described herein provide a device, system and methodfor the transdermal iontophoretic delivery of various therapeuticagents. As used herein, the term transdermal delivery refers to thedelivery of a compound, such as a drug or other therapeutic agent,through one or more layers of the skin (e.g., epidermis, dermis, etc).Referring now to FIG. 1, the layers of the skin include the epidermisEP, dermis D and subdermis SD. The upper most layer of the epidermisincludes the stratum corneum SC, a dead layer of skin (having athickness of about 10 to 40 μm) and the viable epidermis EP. Transdermaldelivery can proceed by one of the three passage ways into the skin, via1, the sweat pores SP, 2, the hair follicles HF or via permeation 3through the epidermis EP (starting at the stratum corneum) and thedermis.

Iontophoresis is a non-invasive method of propelling high concentrationsof a charged substance, known as the active agent, transdermally byrepulsive electromotive force using a small electrical charge. Theactive agent can include a drug or other therapeutic agent. The chargeis applied by an electrical power source to an active electrode assemblyplaced on the skin which contains a similarly charged active agent and asolvent in which it is dissolved. Current flows from the electrodeassembly through the skin and then returns by means of a return orcounter electrode assembly also placed on the skin. A positively chargedelectrode assembly, termed the anode will repel a positively chargedactive agent, or anion, into the skin, while a negatively chargedelectrode assembly, termed the cathode, will repel a negatively chargedactive agent, known as a cation into the skin.

Referring now to FIGS. 2-5, an embodiment of a system 5 for thetransdermal iontophoretic delivery of a therapeutic agent 51 to a tissuesite TS (such as the arm A) also referred to as a delivery site, on theskin S of patient, comprises at least two electrode assemblies 14 (FIG.5) including an active electrode assembly 20 and a return electrodeassembly 30; and a power supply 100. Active electrode assembly 20 isused to deliver the therapeutic agent through skin S via currentdelivered to the skin from power supply 100. Return electrode assembly30 provides a return path for current to power supply 100. Collectively,the active and return electrode assemblies 20 and 30 comprise atransdermal iontophoretic delivery device 10 also described herein aspatch device 10. In embodiments using an alternating current, bothelectrode assemblies 14 can be configured as active and return electrodeassemblies 20 and 30 depending on the direction of current flow. In somecases for sake of brevity, electrode assembly 14, active electrodeassembly 20 and/or return electrode assembly 30 will sometimes bereferred to as electrode 14, active electrode 20 and return electrode30.

In many embodiments, the electrode assemblies 14 (e.g., active andreturn assemblies 20 and 30) comprise or are otherwise disposed on oneor more patches 15 configured to be applied to the skin surface. Patches15 are conformable to a contour CR of a skin surface S and can befabricated from layers of elastomeric or other flexible polymermaterial. In some embodiments, two or more electrode assemblies 14including active and return electrode assemblies 20 and 30 can be placedon a single patch 15. In other embodiments, system 5 can includeseparate patches 15 for electrode assemblies 14, for example, a firstpatch 15′ for the active electrode assembly 20 and a second patch 15″for the return electrode assembly 30. In other embodiments, three ormore patches 15 can be used so as to have either multiple activeelectrode assemblies 20 or return electrode assemblies 30 or both. Forexample, in one embodiment system 5 can comprise three patches 15;including two patches containing active electrode assemblies 20 and athird patch 15 containing a return electrode assembly 30. Othercombinations of multiple patches and electrode assemblies are alsocontemplated, e.g., four patches, two for active electrode assemblies 20and two for return electrode assemblies 30.

In many embodiments, active electrode assembly 20 can comprise areservoir 21 for the therapeutic agent, a tissue contacting porousportion 24 in fluidic communication with the reservoir, an adhesiveportion 25 for adhering the assembly to the skin, and an electricalconnector 26 for coupling the electrode assembly 20 to an electricalpower supply 100 as is shown in the embodiment of FIG. 4 a. Reservoir 21can be sized for the particular dose of therapeutic agent to bedelivered. In various embodiments, the power supply 100 can includevarious features to facilitate use by medical personnel both in ahospital setting and in the field. For example, the power supply caninclude or be configured to be coupled to a bar code reader (not shown)for reading bar codes positioned on one or more of electrode assemblies14, patches 15 or power supply 100.

Tissue contacting portion 24 is also conductive by virtue of beingfabricated from conductive porous materials (e.g., conductive fibers) orbecomes conductive by becoming wetted with conductive solution 54 (theconductivity being due to agent 51 or various electrolytes added to thesolution) and thus functions as an electrode 20. Connector 26 can extendinto or otherwise make electrical contact with tissue contacting portion24. In some embodiments, connector 26 can be coupled to a conductiveelement 28 positioned within the electrode assembly 20 and coupled toconductive porous portion 24. One or more of conductive element 28,conductive layer 34 (described below) as well as lateral electrodes 40(also described below) can comprise various conductive materialsincluding stainless steel, carbon, AgCl or other conductive materialsknown in the art.

Typically, the therapeutic agent 51 will be dissolved in a therapeuticagent solution 54, also described as therapeutic agent composition 54which is used to fill reservoir 21. In addition to agent 51, solution 54can include one or more pharmaceutical excipients 52 such aspreservatives. The viscosity of the solution 54 can be adjusted to havethe solution readily wick from reservoir 21 into porous layer 24.Solution 54 can be preloaded into the reservoir 21 at the factory or canbe added by medical personnel prior to use through means of a port 22,such as self sealing port allowing injection which is coupled toreservoir 21 via means of a channel 27 as is shown in the embodiment ofFIG. 3 b. Suitable therapeutic agents 51 can include without limitationferric pyrophosphate or other iron containing compound for the treatmentof iron deficient anemia, insulin or various glucagon like peptides fortreatment of diabetes or other blood sugar regulation disorder, Fentanylor other opioid compound for pain management and variouschemotherapeutic agents for the treatment of cancer such as Paclitaxel.

The return electrode assembly 30 comprises a tissue contactingconductive layer 34, an adhesive layer 35 and a connector 26 forcoupling the electrode assembly to the electrical power source. In manyembodiments, the return electrode assembly 30 can have substantially thesame elemental configuration as active electrode assembly 20 (e.g., areservoir 21, conductive tissue contacting layer 24) so as to functionas an active electrode assembly as is shown in the embodiment of FIG. 3b.

In many embodiments, patch 15 also includes one or more pair ofelectrodes known as lateral electrodes 40. Lateral electrodes 40 can beplaced on either side of porous portion 24 at a selectable distance fromthe perimeter 24 p of porous portion 24 as is shown in the embodimentsof FIGS. 3 a-3 b and 4 a-4 b. Electrodes 40 can comprise variousconductive materials including metals, graphite, silver chloride andother like materials. In various embodiments, all or a portion ofelectrode 40 can include an insulative coating so as to be acapacitively coupled electrode that delivers current to the skin viacapacitive coupling. Electrodes 40 can be electrically isolated fromelectrodes 20 and 30 will typically include their own wave formgenerator circuits.

The lateral electrodes 40 are arranged with respect to porous portion 24such that they result in a conductive pathway 104 which goes through theskin S underlying portion 24 and is substantially parallel to the skin.Embodiments of patch 15 that employ lateral electrodes 40 with deliveryelectrodes 20, allow for the flow of two currents, a first current 60and a second current 70. First current 60 flows between electrodes 20and 30 and serves to provide an electromotive force which acts to drivethe therapeutic agent 51 into and across the layers of the skin S. Thesecond current 70, known as sieving current 70, provides anelectromotive force that acts on the therapeutic agent 51 in a directionparallel to the skin S so as to cause oscillation of therapeutic agent51 in a direction parallel to skin S. This oscillation acts to sieve thetherapeutic agent through pathways of lesser or least diffusionalresistance in the skin. For embodiments where second patch 15″ containslateral electrodes 40 and is used to deliver therapeutic agent, a thirdcurrent 70′ can be delivered from lateral electrodes on the second patch15″ to also create a electromotive driving force 80 to oscillate thetherapeutic agent substantially parallel to the skin surface underneaththe second patch 15″. Further description on the arrangement and use oflateral electrodes 40 including use in generating a sieving current isfound in U.S. Provisional Patent Application Serial No's. 61/152,251 and61/221,010 which are incorporated by reference herein in their entirety.

Referring now to FIGS. 5-6, embodiments of a power control architecture105 for optimizing power supplied to a transdermal iontophoreticdelivery system 5 will now be described. Architecture 105 can beconfigured to optimize power used by system 5 for iontophoretic drugdelivery to a patient at a delivery site such as the skin or other siteon or within the body (e.g., the eye, the tympanic membrane, buccalmucosa, intestinal mucosa, etc.). This, in turn, reduces powerconsumption and extends battery life of system 5 or other transdermaliontophoretic delivery system. Accordingly, embodiments of thearchitecture are particularly useful for extending the battery life fortransdermal iontophoretic delivery systems.

Architecture 105 will typically comprise a power supply 100, at leasttwo electrodes 14 (e.g., an active and return electrode), a controller110, a current source 130, a current/impedance measurement device 140and at least one switch 150. Many variations to this configuration arealso contemplated, including for example, the inclusion of additionalelectrodes, sensors, filters (e.g., high pass, low pass, band pass,etc.), communication devices (e.g., an RF ID chip), various powermanagement devices and other electronic devices and circuitry. All orportions of architecture 105 can be fabricated or otherwise positionedon a single integrated circuit (e.g., an ASIC or application specificintegrated circuit) or on multiple integrated circuits (e.g., a chipset) that are operably coupled. All or portions of architecture 105 cancomprise an iontophoretic delivery circuit 106 for iontophoretic drugdelivery. Typically, circuit 106 comprises power source 100,patch/electrode(s) 14 and the patient's skin/tissue at delivery site TS.

Power supply 100 will typically include at least one voltage source 120such as a portable battery or other electrical storage means coupled toa voltage converter 125. Suitable portable batteries include lithium,lithium ion, alkaline, or zinc-air battery with other chemistries alsocontemplated. As an alternative, voltage source 120 may, in variousembodiments, comprise a capacitor (or other electrical storage means) oran energy harvesting device (e.g., a piezoelectric device) alone or incombination with another electrical storage means (e.g., a battery,capacitor, etc.). Voltage converter 125 serves to convert a voltage 121from voltage source 120 to a desired voltage output voltage 127 used byarchitecture 105 and/or other circuitry and electrical components ofsystem 5. Converter 125 can be fixed (e.g., step down, or step up) orvariable and may be controllable by analog or digital inputs, e.g., fromcontroller 110 or a manual input. The converter 125 can comprise varioussolid state devices (e.g., an integrated circuit) known in the art.

In many embodiments, power supply 100 can comprise a variable powersupply 100 t which may be controlled by a controller 110 or othercontrol means (e.g., a remote controller). In an exemplary embodiment,variable power supply 100 t comprises a portable battery 120 and avariable voltage converter 125 that is controllable by inputs 126 fromcontroller 110. Inputs 126 can comprise digital or analog inputs (or acombination thereof), depending upon choice of a digital or analogcontroller 110. In this and related embodiments, converter 125 can beused to convert battery voltage 121 in the range from about 1.5 to 9volts to an output voltage 127 in the range of about 10 to 100 volts,with other ranges also contemplated.

Controller 110 is used to control one or more electrical parameters ofsystem 10 including the iontophoretic driving voltage and deliverycurrent. Typically, it will be operably coupled to one or more of powersupply 100, voltage converter 125, current source 130 and measurementdevice 140. It may also be coupled to or even integral with one or moreother electrical devices, circuitry, sensors, electrodes (e.g.,electrodes 20 and 30), communication devices (e.g., an RF chip) andother related components. Controller 110 includes or is otherwiseconfigured to implement logic for utilizing an input such as input 147from measurement device 140, to generate an output signal such as single126 to minimize power drawn from power supply 100 including battery 110while maintaining the current used by circuit 106 above a thresholdlevel. In this way, battery life can be extended during periods ofiontophoretic transdermal drug delivery utilizing circuit 106. Suchlogic can be incorporated into one or more software modules 115described herein.

In various embodiments, controller 110 can comprise a microprocessor,ASIC, state machine or other logic resource known in the art and isconfigured to perform one or more control functions for architecture105. In preferred embodiments, controller 110 comprises a digitallybased controller such as a microprocessor. In some embodiments,controller 110 may include one or more control modules 115 that comprisea software program, subroutine or other electronic instruction setdigitally stored within controller 110 or memory device 117 or othermemory resources 118 coupled to controller 110. Modules 115 can beconfigured to control one or more electrical parameters of architecture105 and system 5 including various voltages, currents (e.g., aniontophoretic delivery current), duty cycles, total delivered currentand like parameters. Modules 115 can be pre-stored in controller 110 ordownloaded from a memory device 117 coupled to the controller 110 orfrom a separate computer or the internet or other distributed network.In various embodiments, a physician or other medical caregiver candownload one more modules 115 (corresponding to one or more drugdelivery regimens) wirelessly using the internet and a portable wirelesscommunication device such as a cell phone or tablet based device such asthe Apple® Ipad®.

Current source 130 is used to control the current 132, also known asiontophoretic delivery current 132 (herein delivery current) deliveredto electrode assemblies 20. Current source 130 is typically acontrollable current source and may be controlled by one or more inputs132 (digital, analog or a combination) from controller 110 or othercontrol means. Accordingly, current source 130 may comprise variouscontrollable current sources known in the art including variousdigitally controlled programmable current sources. Switch 150 is used tocontrol the direction of current flow from current source 130 and maycorrespond to an H-bridge and other devices known in the art forcontrolling the direction of current flow.

Current measurement device 140 is configured to measure theiontophoretic delivery current delivered to the patient. It typicallycomprises a resistor 141, (also described as R2) an op-amp device 143and an analog to digital (AD) converter 144. As shown in the embodimentof FIG. 5, device 140 functions by measuring a voltage across a knownresistor and then digitally converting that signal which is then fedinto controller 110. Specifically, a voltage 145 across resistor R2, 141is fed into op-amp device 143, with the output 146, digitally convertedby A/D (Analog to Digital) converter 144 into a digital signal 147 thatis inputted into controller 110. Controller can then convert signal 147into a current by applying ohms law (I=V/R). Other configurations formeasuring current 132 are also contemplated. In an alternativeembodiment, measurement device 140 can be an impedance measurementdevice that has a similar configuration to current measurement device140 so as to measure tissue impedance (e.g., the impedance betweenelectrode assemblies 14) over a range of frequencies, such as forexample from about 0.01 to 1000 hz, and digitally convert that outputsignal into a digital signal 147 that is fed into control 110.

According to one or more embodiments of methods of using architecture105, prior to or during a period of intophoretic drug delivery,controller 110 sends a signal 111 to set current source 130 to a desiredoutput delivery current 131. The actual current 132, delivered fromcurrent source 130 is then measured by measurement device 140 by sensingthe voltage across series resistor 141, R2 and then applying ohms law(I=V/R). Controller 110 then compares the actual and desired currents132 and 131 and sends a signal 126 to voltage converter 125 to changethe output voltage 127 to obtain the desired delivery current 131. Inaddition, or as a supplement to use of current 132, controller 110 mayuse other various electrical parameters of architecture 105, anddelivery circuit 106 as an input to modify the iontophoretic deliverycurrent. Such parameters can include without limitation, the totalresistance/impedance of architecture 105 and the totalresistance/impedance R1 between electrodes 14 and/or the tissueimpedance at the delivery site TS. The latter value can be obtained byuse of a sensor placed on or in the skin at the delivery site TS. Insome embodiments, the sensor can comprise electrode 14, such as activeelectrode 20.

The control algorithm used by controller 110 for controlling current 132may comprise one or more of a proportional (P), integral (I), derivative(D), PI, or PID based algorithm. Additionally, the control algorithm maybe included in a software module 115 resident within controller 110 asis described herein.

R1 is a lumped resistance representing the impedance between theelectrode assemblies 14 (e.g., active and electrode assemblies 20 and30). The lumped resistance R1 comprises the resistance/impedance of theskin and other tissue through which iontophoretic current from currentsource 130 passes. The total voltage, VST required is the sum of all thevoltage drops across the components of architecture 105. These voltagesare depicted as VST, VR1, VCS, and VR2 as is shown in the embodiment ofFIG. 5. Ideally though not necessarily, the voltage required by theload, VR1, is large compared to the other voltages (e.g., VCS, VR2 etc).

In particular embodiments for optimal power efficiency, Vt may be set toapproximately the sum, or slightly above the sum, of the values of VR1,VCS, and VR2. Table 1, illustrates the power savings for aniontophoretic delivery system 5/device 10 that is achieved through useof power optimization methods described herein for various currents andimpedance loads. As shown in the table, power saving of 59% or more canbe achieved.

TABLE 1 Vt with Vt without optimal Programmed Load Required optimalenergy Current Impedance Stimulation energy method Power (mA) (Ohms)Voltage (V) method (V) (V) Savings 2 20000 40 80 44 45% 3 10000 30 80 3359% 3 25000 75 80 80 0

FIG. 6 illustrates an embodiment of a power optimization algorithm 200for implementing methods for optimizing power used for the iontophoreticdelivery of a therapeutic agent to a patient. These and related methodscan be implemented using an embodiment of architecture 105 or relatedpower optimization architecture. However, other architectures are alsocontemplated. It should be appreciated that the order of these steps inthe algorithm is exemplary and that the steps need not be done in thesequence described. Also only a portion of the steps in the algorithmneed be used and others can be added or substituted. For example, asdescribed below, a current measurement step can be substituted with animpedance measurement step.

In a step 300, a target iontophoretic delivery current is set bycommunication from controller 110 to the current source 120. Then in astep 310 a driving voltage is set to an initial value by communicationfrom controller 110 to voltage converter 135. Then in a step 320 currentis delivered to the patient and in step 330 the delivered current ismeasured using current/voltage measurement device 140. As an alternativeto current measurement, step 330 may comprise an impedance measurementstep. The impedance that can be measured can include one or more of thetotal impedance of system 5, the total impedance between electrodes 14and the tissue impedance at the drug delivery site. The measured anddesired current (or impedance) are compared in a step 340. If themeasured current or impedance is not at the desired level, thedriving/stimulations voltage is increased in a step 350. If the currentis at the desire level, then the algorithm waits a predetermined amountof time, in a wait step 360 before decreasing the driving/stimulationvoltage in step 370. The wait period can be in the range from about0.001 to 10 seconds or longer. After step 370, the algorithm then cyclesback to current measurement step 330. This cycle can then be repeatedthroughout the entire period of iontophoretic current delivery in asubstantially continuous fashion or for a selected portion thereof.Examples of measuring the electrical property for selected portions oftime include variable or fixed intervals in the range of about 0.001 to1.0 second, and/or where periods between intervals may span the range ofabout 0.001 to 1.0 second. Moreover, the electrical property may bemeasured before and during the period current is delivered to the skin.The amount that the stimulating voltage is decreased or increased insteps 350 and 370 can range from about 0.01 to about 10% of thestimulating voltage with lower and higher values contemplated. Inspecific embodiments, the amount of voltage increase or decrease can be0.05, 0.1, 0.25, 0.5, 1, 5, or 7.5% of the stimulating voltage. Theamount of voltage increase or decrease can itself vary depending uponone or more variables such as the initial stimulation voltage levels,impedance levels and/or a user input.

CONCLUSION

The foregoing description of various embodiments of the invention hasbeen presented for purposes of illustration and description. It is notintended to limit the invention to the precise forms disclosed. Manymodifications, variations and refinements will be apparent topractitioners skilled in the art. For example, the iontophoretic patchcan be modified in size, shape and dose of therapeutic agent fordifferent medical conditions, different tissue sites as well as forvarious pediatric applications. Additionally, the power optimizationalgorithm can also be modified for skin type, therapeutic agent dose, aswell as various pediatric applications.

Elements, characteristics, or acts from one embodiment can be readilyrecombined or substituted with one or more elements, characteristics oracts from other embodiments to form numerous additional embodimentswithin the scope of the invention. Moreover, elements that are shown ordescribed as being combined with other elements, can, in variousembodiments, exist as standalone elements. Hence, the scope of thepresent invention is not limited to the specifics of the describedembodiments, but is instead limited solely by the appended claims.

1. A method for optimizing power for the iontophoretic transdermaldelivery of a therapeutic agent to a patient in need thereof, the methodcomprising: applying a patch to the skin of the patient, the patchcomprising a therapeutic agent and at least one electrode; coupling theat least one electrode to a power source; delivering a selected currentto the skin from the patch to transport the therapeutic agent into theskin; measuring an electrical property of a circuit comprising thepatient and the power source; and adjusting a voltage responsive to themeasured electrical property, wherein the voltage is adjusted tomaintain the selected current while minimizing power delivered from thepower source.
 2. The method of claim 1, wherein power from the powersource is reduced by up to about 45 percent by adjustment of thevoltage.
 3. The method of claim 1, wherein power from the power sourceis reduced by up to about 60 percent by adjustment of the voltage. 4.The method of claim 1, wherein the therapeutic agent comprises an ironcontaining compound for the treatment of iron deficiency anemia.
 5. Themethod of claim 1, wherein the therapeutic agent comprises insulin or aglucagon like peptide for the treatment of a blood sugar regulationdisorder.
 6. The method of claim 1, wherein the therapeutic agentcomprises Fentanyl or an opioid for pain management.
 7. The method ofclaim 1, wherein the electrical property is one of a skin impedance, askin resistance, a lumped impedance, a lumped resistance or a deliveredcurrent.
 8. The method of claim 1, wherein the power source is anelectrochemical battery and battery life is extended by adjustment ofthe voltage.
 9. The method of claim 8, wherein the battery is a lithiumor alkaline battery.
 10. The method of claim 8, wherein a batteryvoltage or current is maintained above a minimum level for a therapeuticagent delivery period as a result of the minimized delivered power. 11.The method of claim 10, wherein the delivery period is up to about oneweek.
 12. The method of claim 10, wherein the delivery period is up toabout two weeks.
 13. The method of claim 1, wherein the current is analternating current.
 14. The method of claim 8, wherein the current hasa frequency in a range from about 0.5 to 100 hz.
 15. The method of claim1, wherein the electrical property is measured over a range offrequencies.
 16. The method of claim 10, wherein the range offrequencies is from about 0.01 to about 1000 hz.
 17. The method of claim1, wherein the voltage is adjusted using a controller.
 18. The method ofclaim 17, wherein the controller is an analog device, a state machine, adigital controller or a microprocessor.
 19. The method of claim 17,wherein the controller utilizes a software module to adjust the voltage.20. The method of claim 1, wherein the electrical property is measuredusing a sensor.
 21. The method of claim 20, wherein the sensor iscoupled to at least one of the power source or a controller coupled tothe power source.
 22. The method of claim 20, wherein the sensor ispositioned on or in the patch.
 23. The method of claim 20, wherein thesensor comprises the at least one electrode.
 24. The method of claim 1,wherein the electrical property is measured in a substantiallycontinuous fashion during the period current is delivered to the skin.25. The method of claim 1, wherein the electrical property is measuredat fixed intervals during the period current is delivered to the skin.26. The method of claim 25, wherein an interval duration is in a rangeof about 0.001 to 1 seconds.
 27. The method of claim 25, wherein aperiod between intervals is in a range of about 0.001 to 1 second.
 28. Amethod for optimizing power for the iontophoretic transdermal deliveryof a therapeutic agent to a patient in need thereof, the methodcomprising: applying a patch to the skin of the patient, the patchcomprising a therapeutic agent and at least one electrode; coupling theat least one electrode to a power source; delivering a selected currentto the skin from the patch to transport the therapeutic agent into theskin; measuring an electrical impedance of the patient; and adjusting avoltage responsive to the measured impedance, wherein the voltage isadjusted to maintain the selected current while minimizing powerdelivered from the power source.
 29. The method of claim 28, wherein theimpedance is measured in a volume of tissue between the at least oneelectrode and a return electrode applied to the skin of the patient. 30.The method of claim 28, wherein the impedance is measured in a circuitcomprising at least two of the at the least one electrode, the patient'stissue and the power source.
 31. A architecture for optimizing power forthe iontophoretic transdermal delivery of a therapeutic agent to apatient in need thereof, the architecture comprising: a first and secondelectrode, at least one of the electrodes operably coupled to aiontphoretic transdermal patch for delivering the therapeutic agent tothe patient; a power source operably coupled with the first and secondelectrodes, the power source comprising a voltage source and a voltageconverter operably coupled to the voltage source; a current sourceoperably coupled to at least one of the first and second electrodes; ameasurement device operably coupled to the current source; and acontroller operably coupled to the measurement device and the voltageregulator, the controller including logic for utilizing an input fromthe measurement device to generate an output sent to the voltageregulator so as to maintain current from the current source above athreshold level while minimizing power drawn from the power source. 32.The architecture of claim 31, wherein the measurement device is one ofan impedance measurement device or a current measurement device.
 33. Thearchitecture of claim 31, wherein the controller is a microprocessor.34. The architecture of claim 33, wherein the controller logic isincorporated into a software module operable by the controller.
 35. Thearchitecture of claim 31, wherein the voltage source is one of anelectrochemical storage battery, a lithium battery or an alkalinebattery.
 36. The architecture of claim 31, wherein at least twocomponents of the architecture are fabricated on a single integratedcircuit.
 37. The architecture of claim 36, wherein the integratedcircuit is an ASIC.
 38. The architecture of claim 31, wherein thecontroller logic is configured to generate an output sent to the currentsource for controlling current from the current source.
 39. Thearchitecture of claim 31, wherein the measurement devices comprises aresistor and an op-amp.
 40. The architecture of claim 39, wherein themeasurement devices further comprises an A/D converter.